tbuckley/cabot-search huggingface dataset:
Author Correction: Skeletal and extraskeletal disorders of biomineralization
Authors: Michael T. Collins, Gemma Marcucci, Hans-Joachim Anders, Giovanni Beltrami, Jane A. Cauley, Peter R. Ebeling, Rajiv Kumar, Agnès Linglart, Luca Sangiorgi, Dwight A. Towler, Ria Weston, Michael. P. Whyte, Maria Luisa Brandi, Bart Clarke, Rajesh V. Thakker
Journal: Nature Reviews Endocrinology (2022)
Ocular Monkeypox — United States, July–September 2022
Authors: Shama Cash-Goldwasser, Sarah M. Labuda, David W. McCormick, Agam K. Rao, Andrea M. McCollum, Brett W. Petersen, James Chodosh, Catherine M. Brown, Suk Yin Chan-Colenbrander, Caitlin M. Dugdale, Michael Fischer, Amy Forrester, Jayne Griffith, Rachel Harold, Bruce W. Furness, Vivian Huang, Aaron R. Kaufman, Ellen Kitchell, Rachel Lee, Nicholas Lehnertz, Ruth Lynfield, Ketzela Jacobowitz Marsh, Lawrence C. Madoff, Nelson Nicolasora, Dharmendra Patel, Roberto Pineda, Trey Powrzanas, Afsoon Roberts, Maria Teresa Seville, Ami Shah, Joshua M. Wong, Jana M. Ritter, Caroline A. Schrodt, Elliot Raizes, Sapna Bamrah Morris, Jeremy A. W. Gold, Amimah Asif, Amy Beeson, Ramon Bhatia, Brian F. Borah, Kevin Chatham-Stevens, Rewa Choudhary, Eleanor Click, Thomas D. Filardo, Romeo R. Galang, Julia Haston, Sophia Hsu, Gurpreet Kaur, Anne Kimball, James T. Lee, Grace Marx, Janet McNicholl, Maureen J. Miller, Rebecca Noe, Siobhan O’Connor, Kevin O’Laughlin, Kia Padgett, Gail Thompson, Farrell Tobolowsky, Isaac Zulu
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

As of October 11, 2022, a total of 26,577 monkeypox cases had been reported in the United States.* Although most cases of monkeypox are self-limited, lesions that involve anatomically vulnerable sites can cause complications. Ocular monkeypox can occur when Monkeypox virus (MPXV) is introduced into the eye (e.g., from autoinoculation), potentially causing conjunctivitis, blepharitis, keratitis, and loss of vision (1). This report describes five patients who acquired ocular monkeypox during July-September 2022. All patients received treatment with tecovirimat (Tpoxx)†; four also received topical trifluridine (Viroptic).§ Two patients had HIV-associated immunocompromise and experienced delays between clinical presentation with monkeypox and initiation of monkeypox-directed treatment. Four patients were hospitalized, and one experienced marked vision impairment. To decrease the risk for autoinoculation, persons with monkeypox should be advised to practice hand hygiene and to avoid touching their eyes, which includes refraining from using contact lenses (2). Health care providers and public health practitioners should be aware that ocular monkeypox, although rare, is a sight-threatening condition. Patients with signs and symptoms compatible with ocular monkeypox should be considered for urgent ophthalmologic evaluation and initiation of monkeypox-directed treatment. Public health officials should be promptly notified of cases of ocular monkeypox. Increased clinician awareness of ocular monkeypox and of approaches to prevention, diagnosis, and treatment might reduce associated morbidity.
Author Correction: Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy
Authors: Melody Smith, Anqi Dai, Guido Ghilardi, Kimberly V. Amelsberg, Sean M. Devlin, Raymone Pajarillo, John B. Slingerland, Silvia Beghi, Pamela S. Herrera, Paul Giardina, Annelie Clurman, Emmanuel Dwomoh, Gabriel Armijo, Antonio L. C. Gomes, Eric R. Littmann, Jonas Schluter, Emily Fontana, Ying Taur, Jae H. Park, Maria Lia Palomba, Elizabeth Halton, Josel Ruiz, Tania Jain, Martina Pennisi, Aishat Olaide Afuye, Miguel-Angel Perales, Craig W. Freyer, Alfred Garfall, Shannon Gier, Sunita Nasta, Daniel Landsburg, James Gerson, Jakub Svoboda, Justin Cross, Elise A. Chong, Sergio Giralt, Saar I. Gill, Isabelle Riviere, David L. Porter, Stephen J. Schuster, Michel Sadelain, Noelle Frey, Renier J. Brentjens, Carl H. June, Eric G. Pamer, Jonathan U. Peled, Andrea Facciabene, Marcel R. M. van den Brink, Marco Ruella
Journal: Nature Medicine (2022)
Author Correction: Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial
Authors: Tien Dam, Adam L. Boxer, Lawrence I. Golbe, Günter U. Höglinger, Huw R. Morris, Irene Litvan, Anthony E. Lang, Jean-Christophe Corvol, Ikuko Aiba, Michael Grundman, Lili Yang, Beth Tidemann-Miller, Joseph Kupferman, Kristine Harper, Kubra Kamisoglu, Michael J. Wald, Danielle L. Graham, Liz Gedney, John O’Gorman, Samantha Budd Haeberlein, Ikuko Aiba, Angelo Antonini, Diana Apetauerova, Jean-Philippe Azulay, Ernest Balaguer Martinez, Jee Bang, Paolo Barone, Matthew Barrett, Danny Bega, Daniela Berg, Koldo Berganzo Corrales, Yvette Bordelon, Adam L. Boxer, Moritz Brandt, Norbert Brueggemann, Giovanni Castelnovo, Roberto Ceravolo, Rosalind Chuang, Sun Ju Chung, Alistair Church, Jean-Christophe Corvol, Paola Cudia, Marian Dale, Luc Defebvre, Sophie Drapier, Erika D. Driver-Dunckley, Georg Ebersbach, Karla M. Eggert, Aaron Ellenbogen, Alexandre Eusebio, Andrew H. Evans, Natalia Fedorova, Elizabeth Finger, Alexandra Foubert-Samier, Boyd Ghosh, Lawrence Golbe, Francisco Grandas Perez, Murray Grossman, Deborah Hall, Kyoko Hamada, Kazuko Hasegawa, Guenter Hoeglinger, Lawrence Honig, David Houghton, Xuemei Huang, Stuart Isaacson, SeongBeom Koh, Jaime Kulisevsky Bojarski, Anthony E. Lang, Peter Nigel Leigh, Irene Litvan, Juan Jose Lopez Lozano, Jose Luis Lopez-Sendon Moreno, Albert Christian Ludolph, Ma Rosario Luquin Piudo, Irene Martinez Torres, Nikolaus McFarland, Wassilios Meissner, Tiago Mestre, Pablo Mir Rivera, Eric Molho, Britt Mollenhauer, Huw R. Morris, Miho Murata, Tomokazu Obi, Fabienne Ory Magne, Padraig O’Suilleabhain, Rajesh Pahwa, Alexander Pantelyat, Nicola Pavese, Dmitry Pokhabov, Johannes Prudlo, Federico Rodriguez-Porcel, James Rowe, Joseph Savitt, Alfons Schnitzler, Joerg B. Schulz, Klaus Seppi, Binit Shah, Holly Shill, David Shprecher, Maria Stamelou, Malcolm Steiger, Yuji Takahashi, Hiroshi Takigawa, Carmela Tartaglia, Lars Toenges, Daniel Truong, Winona Tse, Paul Tuite, Dieter Volc, Anne-Marie A. Wills, Dirk Woitalla, Tao Xie, Tatsuhiko Yuasa, Sarah Elizabeth Zauber, Theresa Zesiewicz
Journal: Nature Medicine (2022)
A Theranostic Approach for CAR-T Cell Therapy
Authors: Wolfgang A. Weber, Zohreh Varasteh, Katja Fritschle, Volker Morath
Journal: Clinical Cancer Research (2022)

Summary Fibroblast activation protein (FAP) is frequently expressed in the tumor stroma, whereas expression by normal organs is highly restricted. Despite these promising features, FAP-targeted therapies have shown limited success so far. FAP imaging offers new opportunities to select patients for FAP-targeted therapies and monitor tumor response. See related article by Lee et al., p. 5330
<i>Monkeypox Virus</i> Infection Resulting from an Occupational Needlestick — Florida, 2022
Authors: Rafael Mendoza, Julia K. Petras, Patrick Jenkins, Margaret J. Gorensek, Susan Mableson, Philip A. Lee, Ann Carpenter, Heather Jones, Marie A. de Perio, Zeshan Chisty, Scott Brueck, Agam K. Rao, Johanna S. Salzer, Danielle Stanek, Carina Blackmore
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In August 2022, the Florida Department of Health notified CDC of a nurse who acquired monkeypox through an occupational exposure while providing care to a patient with monkeypox. To date, occupationally acquired Monkeypox virus (MPXV) infections in health care personnel (HCP) have been rarely reported during the 2022 multinational outbreak (1,2). This report describes the first reported U.S. case and recommends approaches for preventing occupationally acquired MPXV infections in HCP.
Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy
Authors: Takamitsu Hattori, Lorenzo Maso, Kiyomi Y. Araki, Akiko Koide, James Hayman, Padma Akkapeddi, Injin Bang, Benjamin G. Neel, Shohei Koide
Journal: Cancer Discovery (2022)

Intracellular oncoproteins can be inhibited with targeted therapy, but responses are not durable. Immune therapies can be curative, but most oncogene-driven tumors are unresponsive to these agents. Fragments of intracellular oncoproteins can act as neoantigens presented by the major histocompatibility complex (MHC), but recognizing minimal differences between oncoproteins and their normal counterparts is challenging. We have established a platform technology that exploits hapten-peptide conjugates generated by covalent inhibitors to create distinct neoantigens that selectively mark cancer cells. Using the FDA-approved covalent inhibitors sotorasib and osimertinib, we developed "HapImmune" antibodies that bind to drug-peptide conjugate/MHC complexes but not to the free drugs. A HapImmune-based bispecific T-cell engager selectively and potently kills sotorasib-resistant lung cancer cells upon sotorasib treatment. Notably, it is effective against KRASG12C-mutant cells with different HLA supertypes, HLA-A*02 and A*03/11, suggesting loosening of MHC restriction. Our strategy creates targetable neoantigens by design, unifying targeted and immune therapies. Targeted therapies against oncoproteins often have dramatic initial efficacy but lack durability. Immunotherapies can be curative, yet most tumors fail to respond. We developed a generalizable technology platform that exploits hapten-peptides generated by covalent inhibitors as neoantigens presented on MHC to enable engineered antibodies to selectively kill drug-resistant cancer cells. See related commentary by Cox et al., p. 19. This article is highlighted in the In This Issue feature, p. 1.
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy
Authors: Fan Yang, Yi Xiao, Jia-Han Ding, Xi Jin, Ding Ma, Da-Qiang Li, Jin-Xiu Shi, Wei Huang, Yi-Ping Wang, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Cell Metabolism (2022)

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration of metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated the multiomics data of our large TNBC cohort (n = 465) to develop the ferroptosis atlas. We discovered that TNBCs had heterogeneous phenotypes in ferroptosis-related metabolites and metabolic pathways. The luminal androgen receptor (LAR) subtype of TNBC was characterized by the upregulation of oxidized phosphatidylethanolamines and glutathione metabolism (especially GPX4), which allowed the utilization of GPX4 inhibitors to induce ferroptosis. Furthermore, we verified that GPX4 inhibition not only induced tumor ferroptosis but also enhanced antitumor immunity. The combination of GPX4 inhibitors and anti-PD1 possessed greater therapeutic efficacy than monotherapy. Clinically, higher GPX4 expression correlated with lower cytolytic scores and worse prognosis in immunotherapy cohorts. Collectively, this study demonstrated the ferroptosis landscape of TNBC and revealed an innovative immunotherapy combination strategy for refractory LAR tumors.
Allelic variation in the Arabidopsis TNL CHS3/CSA1 immune receptor pair reveals two functional cell-death regulatory modes
Authors: Yu Yang, Nak Hyun Kim, Volkan Cevik, Pierre Jacob, Li Wan, Oliver J. Furzer, Jeffery L. Dangl
Journal: Cell Host & Microbe (2022)

Some plant NLR immune receptors are encoded in head-to-head "sensor-executor" pairs that function together. Alleles of the NLR pair CHS3/CSA1 form three clades. The clade 1 sensor CHS3 contains an integrated domain (ID) with homology to regulatory domains, which is lacking in clades 2 and 3. In this study, we defined two cell-death regulatory modes for CHS3/CSA1 pairs. One is mediated by ID domain on clade 1 CHS3, and the other relies on CHS3/CSA1 pairs from all clades detecting perturbation of an associated pattern-recognition receptor (PRR) co-receptor. Our data support the hypothesis that an ancestral Arabidopsis CHS3/CSA1 pair gained a second recognition specificity and regulatory mechanism through ID acquisition while retaining its original specificity as a "guard" against PRR co-receptor perturbation. This likely comes with a cost, since both ID and non-ID alleles of the pair persist in diverse Arabidopsis populations through balancing selection.
Subunit composition, molecular environment, and activation of native TRPC channels encoded by their interactomes
Authors: Astrid Kollewe, Yvonne Schwarz, Katharina Oleinikov, Ahsan Raza, Alexander Haupt, Philipp Wartenberg, Amanda Wyatt, Ulrich Boehm, Fabien Ectors, Wolfgang Bildl, Gerd Zolles, Uwe Schulte, Dieter Bruns, Veit Flockerzi, Bernd Fakler
Journal: Neuron (2022)
The effect of COVID-19 on the home behaviours of people affected by dementia
Authors: Alina-Irina Serban, Eyal Soreq, Payam Barnaghi, Sarah Daniels, Rafael A. Calvo, David J. Sharp
Journal: npj Digital Medicine (2022)

Abstract The COVID-19 pandemic has dramatically altered the behaviour of most of the world’s population, particularly affecting the elderly, including people living with dementia (PLwD). Here we use remote home monitoring technology deployed into 31 homes of PLwD living in the UK to investigate the effects of COVID-19 on behaviour within the home, including social isolation. The home activity was monitored continuously using unobtrusive sensors for 498 days from 1 December 2019 to 12 April 2021. This period included six distinct pandemic phases with differing public health measures, including three periods of home ‘lockdown’. Linear mixed-effects modelling is used to examine changes in the home activity of PLwD who lived alone or with others. An algorithm is developed to quantify time spent outside the home. Increased home activity is observed from very early in the pandemic, with a significant decrease in the time spent outside produced by the first lockdown. The study demonstrates the effects of COVID-19 lockdown on home behaviours in PLwD and shows how unobtrusive home monitoring can be used to track behaviours relevant to social isolation.
Addressing Gaps in Research to Reduce Disparities and Advance Health Equity
Authors: Carol M. Mangione, Wanda Nicholson, Karina W. Davidson
Journal: JAMA (2022)

This Viewpoint reviews the evidence gaps reported to Congress by the US Preventive Services Task Force (USPSTF) in 2021 on improving health inequities in prevention and uses the 3 taxonomies provided by National Academies of Sciences, Engineering, and Medicine (NASEM) to classify these gaps.
Tumor microenvironment shows an immunological abscopal effect in patients with NSCLC treated with pembrolizumab-radiotherapy combination
Authors: Lieke L van der Woude, Mark A J Gorris, Inge M N Wortel, Jeroen H A Creemers, Kiek Verrijp, Kim Monkhorst, Katrien Grünberg, Michel M van den Heuvel, Johannes Textor, Carl G Figdor, Berber Piet, Willemijn S M E Theelen, I Jolanda M de Vries
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immunotherapy is currently part of the standard of care for patients with advanced-stage non-small cell lung cancer (NSCLC). However, many patients do not respond to this treatment, therefore combination strategies are being explored to increase clinical benefit. The PEMBRO-RT trial combined the therapeutic programmed cell death 1 (PD-1) antibody pembrolizumab with stereotactic body radiation therapy (SBRT) to increase the overall response rate and study the effects on the tumor microenvironment (TME). Methods Here, immune infiltrates in the TME of patients included in the PEMBRO-RT trial were investigated. Tumor biopsies of patients treated with pembrolizumab alone or combined with SBRT (a biopsy of the non-irradiated site) at baseline and during treatment were stained with multiplex immunofluorescence for CD3, CD8, CD20, CD103 and FoxP3 for lymphocytes, pan-cytokeratin for tumors, and HLA-ABC expression was determined. Results The total number of lymphocytes increased significantly after 6 weeks of treatment in the anti-PD-1 group (fold change: 1.87, 95% CI: 1.06 to 3.29) and the anti-PD-1+SBRT group (fold change: 2.29, 95% CI: 1.46 to 3.60). The combination of SBRT and anti-PD-1 induced a 4.87-fold increase (95% CI: 2.45 to 9.68) in CD103 + cytotoxic T-cells 6 weeks on treatment and a 2.56-fold increase (95% CI: 1.03 to 6.36) after anti-PD-1 therapy alone. Responders had a significantly higher number of lymphocytes at baseline than non-responders (fold difference 1.85, 95% CI: 1.04 to 3.29 for anti-PD-1 and fold change 1.93, 95% CI: 1.08 to 3.44 for anti-PD-1+SBRT). Conclusion This explorative study shows that that lymphocyte infiltration in general, instead of the infiltration of a specific lymphocyte subset, is associated with response to therapy in patients with NSCLC. Furthermore, anti-PD-1+SBRT combination therapy induces an immunological abscopal effect in the TME represented by a superior infiltration of cytotoxic T cells as compared with anti-PD-1 monotherapy.
Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia
Authors: Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A. Patel, Sheng F. Cai, Linde A. Miles, Robert L. Bowman, Mark B. Geyer, Andrew Dunbar, Zachary D. Epstein‐Peterson, Erin McGovern, Jessica Schulman, Jacob L. Glass, Justin Taylor, Aaron D. Viny, Eytan M. Stein, Bartlomiej Getta, Maria E. Arcila, Qi Gao, Juliet Barker, Brian C. Shaffer, Esperanza B. Papadopoulos, Boglarka Gyurkocza, Miguel‐Angel Perales, Omar Abdel‐Wahab, Ross L. Levine, Sergio A. Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S. Tallman, Mikhail Roshal, Aaron D. Goldberg
Journal: American Journal of Hematology (2022)

Abstract Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre‐treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre‐treatment next‐generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo‐SCT). Induction chemotherapy led to MRD− remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD‐. Mutations in CEBPA, NRAS , KRAS , and NPM1 predicted high rates of MRD− remission, while mutations in TP53, SF3B1, ASXL1 , and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD− remission. Patients with fewer individual clones were more likely to achieve MRD− remission. Among 132 patients who underwent allo‐SCT, outcomes were favorable whether patients achieved early MRD− after induction or later MRD− after subsequent therapy prior to allo‐SCT. As MRD conversion with chemotherapy prior to allo‐SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.
Weakly supervised inference of personalized heart meshes based on echocardiography videos
Authors: Fabian Laumer, Mounir Amrani, Laura Manduchi, Ami Beuret, Lena Rubi, Alina Dubatovka, Christian M. Matter, Joachim M. Buhmann
Journal: Medical Image Analysis (2022)

Echocardiography provides recordings of the heart chamber size and function and is a central tool for non-invasive diagnosis of heart diseases. It produces high-dimensional video data with substantial stochasticity in the measurements, which frequently prove difficult to interpret. To address this challenge, we propose an automated framework to enable the inference of a high resolution personalized 4D (3D plus time) surface mesh of the cardiac structures from 2D echocardiography video data. Inferring such shape models arises as a key step towards accurate personalized simulation that enables an automated assessment of the cardiac chamber morphology and function. The proposed method is trained using only unpaired echocardiography and heart mesh videos to find a mapping between these distinct visual domains in a self-supervised manner. The resulting model produces personalized 4D heart meshes, which exhibit a high correspondence with the input echocardiography videos. Furthermore, the 4D heart meshes enable the automatic extraction of echocardiographic variables, such as ejection fraction, myocardial muscle mass, and volumetric changes of chamber volumes over time with high temporal resolution.
Utilization of <scp>real‐world</scp> data in assessing treatment effectiveness for diffuse large <scp>B‐cell</scp> lymphoma
Authors: Grzegorz Nowakowski, Matthew J. Maurer, James R. Cerhan, Debarshi Dey, Laurie H. Sehn
Journal: American Journal of Hematology (2022)

Direct comparisons of the effectiveness of the numerous novel therapies in the diffuse large B-cell lymphoma (DLBCL) treatment landscape in a range of head-to-head randomized phase 3 trials would be time-consuming and costly. Comparative effectiveness studies using real-world data (RWD) represent a complementary approach. Recently, several studies of relapsed/refractory (R/R) DLBCL have used RWD to create observational cohorts to compare patient outcomes with cohorts derived from single-arm phase 2 trials. Using propensity score methods to balance clinically and prognostically relevant baseline covariates, closely matched patient-level cohorts can be generated. By incorporating appropriate measures to assess covariate balance and address potential bias in comparative effectiveness study designs, robust comparative analyses can be performed. Results from such studies have been used to supplement regulatory approval of therapies assessed in single-arm trials. While RWD studies have a greater susceptibility to bias compared to randomized controlled trials, well-designed and appropriately analyzed studies can provide complementary real-world evidence on treatment effectiveness.